Recent trends in U.S. urban centers indicate a rise in the number of new HIV infections in the population of young men who have sex with men (YMSM). These trends suggest a high level of vulnerability to HIV seroconversion in YMSM through sexual behavior as they emerge into adulthood. In addition, acts of sexual risk taking in this population often function synergistically with illicit drug use, and mental health burden. Despite some success with HIV prevention in the MSM population during the last 25 years, these recent patterns suggest that a reexamination of our prevention strategies for this population, especially for YMSM of color, is needed. Given the interplay that exists between unprotected sexual behavior, illicit drug use, and mental health burden, all such efforts must consider how these overlapping epidemics (also known as syndemics) fuel each other in a cohort of YMSM as they emerge into adulthood. Thus, we will we will initiate a prospective longitudinal program of research to follow the development of syndemics in a racially/ethnically and economically diverse cohort of urban HIV-negative YMSM in New York City as they transition from adolescence into young adulthood, and apply, test, and further develop a theory of syndemic production to understand the development of both maladaptive and adaptive behavioral outcomes. Specifically we seek to (1) develop and test theoretically informed measurement models of the covariance of illicit drug use, unprotected sexual behavior, and mental health burden among emergent adult HIV-negative YMSM within and across time, (2) assess whether patterns of behavior are continuous, discontinuous, or some combination of both;(3) delineate the risk and protective bases-physical factors (i.e., pubertal onset, HIV status), relational factors (i.e., family history of psychopathology, current romantic relationships, peer support, and characteristics of residential, social, and sex neighborhoods), and psychosocial factors (i.e., sexual identity, internalized homophobia, hypermasculinity, racial identity, racial devaluation, HIV optimism) that predict the development of syndemics, and (4) determine the extent to which the development of syndemics varies by race/ethnicity, social class, and homelessness/housing stability in a cohort of HIV-negative YMSM. Using multiple measurement modalities, which include biological assays, calendar based methods, and self-reports, we will follow the development of 675, 18-year-old HIV-negative YMSM. Participants will be recruited through venue-based and respondent driven sampling, as they emerge into adulthood, over seven waves of data collection within a 36-month time frame. We will utilize Structural Equation and Latent Growth Curve Analysis to answer our four main research questions. PUBLIC HEALTH RELEVANCE: The goal of this project is to understand why a new generation of young men who have sex with other men place themselves at risk for HIV transmission. Knowledge which we will generate will help us understand how these young men emerge into adulthood, the choices they make about sexual behavior and illicit drug use, as well as how these two behaviors interact with their mental health. We seek to understand why some men exhibit risky behaviors as they emerge into adulthood while others do not. Working with community and municipal partners, we will draw from what we have learned from both groups to develop strategies for HIV prevention and intervention that are relevant to this current and developing generation who did not live through the devastation of the AIDS epidemic in the 1980's. In addition, we will add to the methodological literature based on our analysis of nested latent growth curve models.